Antibacterial Paramagnetic Quinones from Actinoallomurus

Four metabolites, designated paramagnetoquinone A, B, C, and D (1–4), were isolated from three strains belonging to the actinomycete genus Actinoallomurus. Compounds 1 and 2 showed potent antibacterial activity with MIC values lower than 0.015 μg/mL against Gram-positive pathogens, including antibiotic-resistant strains. Since compounds 1 and 2 were NMR-silent due to the presence of an oxygen radical, structure elucidation was achieved through a combination of derivatizations, oxidations, and analysis of 13C-labeled compounds. The paramagnetoquinones share the same carbon scaffold as tetracenomycin but carry two quinones and a five-membered lactone fused to the aromatic system. Compounds 2 and 1 are identical except for an unprecedented replacement of a methoxy in 2 by a methylamino group in 1. Related compounds devoid of methyl group(s) and of antibacterial activity were isolated from a different Actinoallomurus strain. The likely pmq biosynthetic gene cluster was identified from strain ID145113. While t...